Stem cell treatment of chronic obstructive pulmonary disease

Stem cell treatment of chronic obstructive pulmonary disease. The lung is a complex organ composed of more than 40 different differentiated types of cells. Different progenitor cell populations are located in different anatomical areas of the adult lung (e.g. lung epithelial stem cells).

Chronic obstructive pulmonary disease (“COPD” for short), or “COPD” for short, is what people often call chronic bronchitis and emphysema. The main symptoms are prolonged cough, sputum and shortness of breath. It is chronic bronchitis and The general term for emphysema. Because of its early onset and concealment, it is easy to be ignored, and it is also called “silent disease”.

What is the cause of chronic obstructive pulmonary disease

Smoking is the most important risk factor for COPD. In addition, indoor and outdoor air pollution, occupational dust and smoke, respiratory infections, genetic factors and long-term asthma are also risk factors for COPD.

The repeated effects of tobacco smoke can cause the accumulation and activation of inflammatory cells and the production of inflammatory mediators, oxidative damage in the body, and directly lead to the occurrence of chronic obstructive pulmonary disease.

It is expected to become the third leading cause of global disease mortality by 2020″. Its current treatment plan aims to relieve symptoms, avoid acute exacerbations, and improve the quality of life of patients, but it cannot prevent its progression or repair damaged lung tissue and function. The mortality of this disease cannot be reduced. Therefore, it is urgent to study new treatment methods for COPD to solve this problem.

The lung is a complex organ composed of more than 40 different differentiated types of cells. Different progenitor cell populations are located in different anatomical regions of adult lungs (such as lung epithelial stem cells). Through animal model experiments and clinical trials, it is found that tissue-specific stem cells and bone marrow-derived stem cells can promote the regeneration of new lung tissue from the injured lung. This suggests that we can treat COPD by giving exogenous stem/progenitor cells or activating endogenous stem/progenitor cells, which is a new feasible treatment plan.

The endogenous stem cell population of the respiratory system

1. The role of airway stem cells

In the lung trachea and the pseudostratified epithelium in the left and right main bronchi, there are basal cells, which are undifferentiated stem cells. Under the action of trophoblast cell surface antigen 2 (TROP2), the proliferation rate of basal cells is significantly increased. Therefore, we It is speculated that TROP2 may be used to promote the differentiation and regeneration of tracheal and bronchial basal cells to achieve the purpose of treating COPD.

2. The role of submucosal bronchial stem cells

The duct cells of the submucosal bronchial glands of the human airway also possess the differentiation characteristics of stem cells by expressing CK5, CK14, p63, etc. on the surface, just like the airway stem cells. Swa-tekAM et al. obtained cells (p63+, CK5+, CK14+) similar to ductal gland stem cells (p63+, CK5+, CK14+) from autopsy lung specimens of patients with bronchiolitis obliterans caused by lung transplantation, and found that the proliferation ability of these stem cells varies with the disease. Progression and decline indicate that the failure of airway submucosal stem cells may be a mechanism of lung failure, which suggests that we can repair ductal gland cells or damaged lung tissue

3. The role of bronchoalveolar stem cells

In the lungs, bronchoalveolar stem cells (BASCs) are only found in the bronchoalveolar ducts. They are in a static state under normal conditions. When the lung is injured, they will proliferate reactively and repair the damaged lung tissue.

4. the role of alveolar stem cells

Researchers found in mouse model experiments that axin-2 (a protein that regulates the stability of β-catenin in the Wnt signaling pathway) can be expressed on the surface of alveolar epithelial type 2 cells, which regulates the self-renewal and lineage specificity of stem cells. Differentiation), and showed the same characteristics as stem cells, including self-renewal ability and the ability to differentiate into alveolar type 1 cells.

5. The role of mesenchymal stem cells in lung tissue

The study found that when cultured in the same environment, mesenchymal stem cells can also promote the proliferation and differentiation of airway epithelial stem cells.

The role of exogenous stem cell populations

At present, some scholars have conducted in-depth research on the effectiveness of exogenous mesenchymal stem cells (marrow mesenchymal stem cells, amniotic fluid mesenchymal stem cells, adipose mesenchymal stem cells, etc.) in the treatment of COPD. Preclinical studies have shown that mesenchymal stem cells (MSCs) can participate in the correction of lung injury caused by COPD through anti-inflammatory, immune regulation, paracrine and tissue repair effects, and promotion of endogenous stem cell proliferation.

1. Anti-inflammatory and immune regulation effects

MSCs affect the innate and adaptive immune system cells, and regulate the balance between proteases and protease inhibitors. The immunomodulatory effects of MSCs include inhibiting the proliferation of T cells and B cells, inducing regulatory B cells and T cells, and making monocytes, macrophages and dendritic cells more prone to anti-inflammatory and tolerant phenotypes. Studies have shown that MSC interacts with macrophages to regulate inflammation.

2. Antibacterial effect

MSCs not only have anti-inflammatory effects but also antimicrobial. These include indirect effects by activating other inflammatory cells to secrete immune mediators, as well as direct inhibition. Experiments have shown that the direct and indirect effects of MSCs may contribute to the host’s defense response to human invading pathogens, which may be related to the prevention or treatment of acute exacerbations of COPD.

3. Paracrine effect

MSCs participate in mediating the secretion of growth factors through the paracrine pathway, and then affect the regeneration of lung tissue cells and vascular endothelial cells. Studies have shown that after treatment with MSCs in COPD patients, the expression of HGF, EGF, VEGF and other mRNA in their bodies increased compared with the control group, and tissue regeneration and repair occurred in the injured lung. These growth factors are thought to help the recovery of lung tissue structure, and the specificity of HGF is related to the anti-apoptotic effect of MSCs. The above mechanism of action has guiding significance for the treatment of COPD.

4. the role of lung tissue repair

The tissue destruction of emphysema is characterized by the loss of alveolar attachment, and MSCs treatment can restore the damaged alveolar structure in an animal model of emphysema. Therefore, we propose that the implantation, human and transdifferentiation of MSCs in epithelial cells contribute to the reconstruction of lung structures damaged in emphysema.

Clinical application and outlook

The degree of differentiation of endogenous stem cells is higher. Whether there are better intervention methods to activate their activity and promote their differentiation into damaged lung tissues still needs further research. In addition, endogenous stem cells are not easy to be isolated and obtained. In contrast. The mechanism of exogenous stem cells is relatively clear, easy to obtain, and the experimental technology is mature. Clinical studies have proved that mesenchymal stem cells have high clinical value in the treatment of COPD. It is hoped that stem cell therapy will bring new dawn to COPD.

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